1. Filed of the Invention
The present invention relates generally to biocompatible polymeric compositions and methods for their production and use. More particularly, the present invention relates to compositions for promoting hemostasis and delivery of bioactive substances.
The ability to inhibit bleeding in a patient (hemostasis) and deliver bioactive substances to the patient (drug delivery) are both of great medical importance. Over the years numerous devices, compositions, and biological agents have been developed for both purposes. As no one device, composition, or approach can fulfill all medical needs, there continues to be a need to provide alternative and improved modalities for achieving both hemostasis and drug delivery.
In particular, it would be desirable to provide new and alternative compositions which are suitable for performing either or both hemostasis and drug delivery to patients. Preferably, such compositions should be a convenient matrix for topical delivery to surgical and/or traumatic wounds to a patient's tissue structures or skin. In particular, such compositions should be dry, be capable of storage for prolonged periods, be in a sheet or other easily manipulable form to facilitate placement, require minimum preparation by a user prior to use, be relatively easy to fabricate, be compatible with the delivery of a wide variety of biological and other active agents, and the like. In the case of hemostatic materials, it would be particularly advantageous to be able to remove excess material without causing further bleeding or other adverse events.
At least some of these objectives will be meet by the embodiments of the invention described hereinafter.
2. Description of the Background Art
Biodegradable injectable drug delivery polymers are described in U.S. Pat. No. 5,384,333 and by Jeong et al. (1997) “Nature,” 388:860–862. Biodegradable hydrogels for controlled released drug delivery are described in U.S. Pat. No. 4,925,677. Resorbable collagen-based drug delivery systems are described in U.S. Pat. Nos. 4,347,234 and 4,291,013.
Aminopolysaccharide-based biocompatible films for drug delivery are described in U.S. Pat. Nos. 5,300,494 and 4,946,870. Water soluble carriers for the delivery of taxol are described in U.S. Pat. No. 5,648,506.
Polymers have been used as carriers of therapeutic agents to effect a localized and sustained release (Langer, et al., Rev. Macro. Chem. Phys., C23(1), 61, 1983; Controlled Drug Delivery, Vol. I and II, Bruck, S. D., (ed.), CRC Press, Boca Raton, Fla., 1983; Leong et al., Adv. Drug Delivery Review, 1:199, 1987). These therapeutic agent delivery systems simulate infusion and offer the potential of enhanced therapeutic efficacy and reduced systemic toxicity.
Other classes of synthetic polymers which have been proposed for controlled release drug delivery include polyesters (Pitt, et al., in Controlled Release of Bioactive Materials, R. Baker, Ed., Academic Press, New York, 1980); polyamides (Sidman, et al., Journal of Membrane Science, 7:227, 1979); polyurethanes (Maser, et al., Journal of Polymer Science, Polymer Symposium, 66:259, 1979); polyorthoesters (Heller, et al., Polymer Engineering Scient, 21:727, 1981); and polyanhydrides (Leong, et al., Biomaterials, 7:364, 1986). U.S. Pat. No. 5,595,735 describes a thrombin paste composition using polyethylene glycols as carriers.
Collagen-containing compositions which have been mechanically disrupted to alter their physical properties are described in U.S. Pat. Nos. 5,428,024; 5,352,715; and 5,204,382. These patents generally relate to fibrillar and insoluble collagens. An injectable collagen composition is described in U.S. Pat. No. 4,803,075. An injectable bone/cartilage composition is described in U.S. Pat. No. 5,516,532. A collagen-based delivery matrix comprising dry particles in the size range from 5 μm to 850 μm which may be suspended in water and which has a particular surface charge density is described in WO 96/39159. A collagen preparation having a particle size from 1 μm to 50 μm useful as an aerosol spray to form a wound dressing is described in U.S. Pat. No. 5,196,185. Other patents describing collagen compositions include U.S. Pat. Nos. 5,672,336 and 5,356,614.
A polymeric, non-erodible hydrogel that may be cross-linked and injected via a syringe is described in WO 96/06883.
The following pending applications, assigned to the assignee of the present application, contain related subject matter: U.S. Ser. No. 09/032,370, filed on Feb. 27, 1998; U.S. Ser. No. 08/903,674, filed on Jul. 31, 1997; U.S. Ser. No. 60/050,437, filed on Jun. 18, 1997; U.S. Ser. No. 08/704,852, filed on Aug. 27, 1996; U.S. Ser. No. 08/673,710, filed Jun. 19, 1996; U.S. Ser. No. 60/011,898, filed Feb. 20, 1996; U.S. Ser. No. 60/006,321, filed on Nov. 7, 1996; U.S. Ser. No. 60/006,322, filed on Nov. 7, 1996; U.S. Ser. No. 60/006,324, filed on Nov. 7, 1996; and U.S. Ser. No. 08/481,712, filed on Jun. 7, 1995. The full disclosures of each of these applications is incorporated herein by reference. WO 98/08550, which claims priority from U.S. Ser. No. 08/903,674, described cross-linked biological polymers which are useful as a component of the materials of the present invention.